Integrated Diagnostic Device

ABSTRACT

A flexible, integrated, urine-based diagnostic device designed such that one or more diagnostic channels are integrated into the body of the device. Each diagnostic channel is designed to contain an immunoassay to detect the presence of a selected analyte so that the device can return a visible readout indicating the presence of the analyte. The flexibility of the device aids the user in the sample collection process.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of U.S.application Ser. No. 15/470,762, filed Mar. 27, 2017, now U.S. Pat. No.10,045,694, which is a continuation application of U.S. application Ser.No. 14/706,159, filed May 7, 2015, now U.S. Pat. No. 9,606,116, whichclaims priority to U.S. provisional patent application No. 61/996,978,filed on May 11, 2014. The contents of these applications areincorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

Urine-based diagnostic devices in their generic form are used in homeand clinical settings for both men and women to test for a wide varietyof conditions and analytes that may be present in urine and other bodyfluids. The devices have been developed to provide for quick, accurate,and easy-to-use testing for people untrained in the field.

Existing devices typically comprise at least two parts: a rigidstructure to serve as a support for the device, and a testing stripwhich carries out the test itself. Such devices use rigid bodystructures, an imprecise specimen collection method (sometimes requiringcounting from the user), singular abstract readout per testing strip (innon-electronic devices), and implied landfill disposal. Urine-baseddiagnostics usually fall into the categories of midstream (device isheld in flowing stream of fluid), dip (device is held in stationaryfluid sample), and cassette (dropper is used to add fluid sample).

The increasing popularity and complexity of these devices have led to anumber of problems. Those of skill in the art will appreciate that atest format remains desirable that integrates the entirety of thedevice, including the user interface, collection portion, and testingportion, into a single format. This would help to simplify themanufacturing process as well as to improving the ease-of-use of thedevice. Additionally, the increase in complexity of existing devices hasenabled such devices to give electronic readouts of the results at theexpense of increasing cost and the requirement of battery operation.Those of skill in the art would appreciate a testing format in which thedevice is able to give both a positive and negative indicator withoutthe use of electronic components remains desirable. This solution wouldbe particularly important as it aids the user experience, reduces cost,simplifies manufacture, and avoids the use of expensive, andnon-biodegradable electronic components. The user experience could beeven further improved by using a visual readout that has a clearerindication than the current non-electronic devices in the market thattypically use one or more lines to indicate the result which are oftendifficult to interpret.

Because these diagnostic devices are often used to obtain sensitive testresults, discretion is typically an important priority for the user.There are a number ways to improve test discretion. For discretion whilecarrying the device, it would be desirable to create a device that isnot only small, but is able to be folded to compact form withoutdamaging the device itself. Additionally, discretion at disposal can beparticularly important where one would not want the device to be found.Therefore, a test format that is completely flushable or waterdispersible would be advantageous. A flushable, water dispersible, orbiodegradable device would also be desirable as it would reducedependency on landfill systems.

Ease-of-use is also important for these types of at-home testing deviceswhich are typically used by untrained people. Typical hand-held devicesare rigid and require aiming of urine on the part of the user, whichtends to be particularly difficult for females. Other devices in thefield attempt to solve this problem by allowing the user to dip the testin a sample, or attach the device to a toilet. Those of skill in the artwould recognize that a device that could aid in sample collection andtesting without first collection of the sample in a separate container,or attaching the device to an object for collection, would beadvantageous to ease the user experience.

BRIEF SUMMARY OF VARIOUS EMBODIMENTS OF THE INVENTION

The present invention is directed to urine-based diagnostic tests andtesting devices that address the above-mentioned and other needs in theart. One embodiment of the device is designed to create a single,integrated, testing device that comprises the user interface, collectionportion, and testing portion that increases the simplicity ofmanufacturing and ease-of-use of the device. In this embodiment, one ormore diagnostic channels are integrated into the device material. Eachdiagnostic channel includes an immunoassay for reacting with an analytein a sample. Additionally, the device itself is flexible such that canbe adjusted to aid in the collection of urine.

Other embodiments of the device include one or more channels having asandwich immunoassay, a competitive immunoassay, or both a competitiveand sandwich immunoassay. In other embodiments, the competitive andsandwich immunoassays are able to give either a positive or negativevisual readout to the user. Other embodiments of the device can beflushable, water dispersible, or biodegradable to both reduce relianceon landfills as well as aiding in keeping the test discrete. In otherembodiments, the device can also be foldable to aid in keeping thedevice discrete as well as to aid in transportation of the product. Inother embodiments, the readout of the device is displayed by text,graphic designs, or symbols to aid in the ease-of-use. Other embodimentsof the device may further include an embossed pattern on the collectionportion of the device to aid in collection and to direct flow of thesample. In further embodiments, the collection portion of the deviceincludes a perforation such that the soiled portion of the device can beremoved after sample collection without affecting the results of thetest.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned and other advantageous features of the inventionwill be apparent from the following detailed description in connectionwith the attached drawings, of which:

FIG. 1 is a perspective view of one embodiment of the device whichincludes a volume indicator, positive indicator, control indicator,tear-line, and embossed collection pad.

FIG. 2 is a perspective view of one embodiment of the device in whichtwo immunoassays are integrated into the device in order to give apositive or negative readout.

FIG. 3 is a perspective view of one embodiment of the device thatincludes a positive readout, a control indicator, a volume indicator, anembossed collection area, and two fold lines.

FIG. 4 is a perspective view of a portion of one embodiment of thedevice wherein the test results are given using written word readouts.

FIG. 5 is a side view of one embodiment of the device where the deviceis opened flat.

FIG. 6 is a side view of one embodiment of the device where the deviceis halfway folded.

FIG. 7 is a side view of one embodiment of the device where the deviceis completely folded.

FIG. 8 is a perspective view of an embodiment of the device thatincludes a control, a first immunoassay, a second immunoassay, and athird immunoassay in the same channel, a volume indicator, two foldlines, and an embossed collection pad.

FIG. 9 is a perspective view of an embodiment of the device wherein thetest results are given using a graphic design.

DETAILED DESCRIPTION

The various embodiments of the present invention are designed asintegrated diagnostic devices wherein the structure, user interface,collection portion, and test portion form a single, easy-to-use, andsimple to manufacture testing device.

One embodiment of the device is illustrated in FIG. 1. This embodimentis an integrated device that comprises a diagnostic channel with animmunoassay 1, a urine volume indicator 2, a control indicator 3, aperforation 4, and an embossed collection pad 5. In one embodiment, thedevice uses microfluidic techniques as the channel system of thediagnostic assay which allows the system to be a single manufacturedobject with the user interface and structure. The device integratesthese attributes into a single material such that the piece that theuser holds, uses, or urinates on is materially integrated with themicrofluidic channels and diagnostic assay. The arrangement of theimmunoassay 1, urine volume indicator 2, and control indicator 3, inFIG. 1 is not the only one contemplated and should not be limited tothis layout. A control indicator 3 is included to provide a visibleindication that the test has run.

In the embodiment illustrated in FIG. 1, the immunoassay can be designedto test for various analytes. For example, in one embodiment theimmunoassay could be designed to test for the hormone hCG which wouldallow the device to return a result with respect to whether the user ispregnant. However, the device can be designed to test for any number ofanalytes present in urine including, but not limited to, hCG-H andvarious drugs (such as cocaine, THC, or amphetamines), glucose, ketones,luteinizing hormone, or hemoglobin. Depending on the analyte chosen, thedevice can be designed to test for various conditions, diseases, orother information including the presence of sexually transmitteddiseases, diabetes, pregnancy, kidney disease, or cancers.

The immunoassays being used in the various embodiments can be designedin a number of different ways. For example, the immunoassay can bedesigned as a “sandwich” assay or a “competitive” assay. Additionally,the immunoassays can be structured to test in a lateral flow or verticalflow format. The type of assay being used will depend on the desiredfunction of the device. For example, persons of skill in the art wouldrecognize that a “sandwich” assay would be useful if one desired thedevice to indicate the presence of an analyte above a predeterminedconcentration while a “competitive” assay would indicate when thedesired analyte is absent at a predetermined level.

The immunoassays can be adhered to the non-woven material of the devicein a number of ways. A simple method for accomplishing this would be toadd a mixture of the biorecognition agents directly to the device in thedesired format and then drying the mixture to adhere it to the device.The biorecognition agent depends on the analyte being tested for and caninclude antibodies, hormones, or other chemicals that detect the targetanalyte. This method of drying antibodies to the device has the addedbenefit of simplicity. However, other methods can be used, such asvarious printing techniques. An example would be to use ink-jetprinting, which a person of ordinary skill would find as useful because,among other reasons, it is a non-impact technique. One example of inkjetprinting that can be used is through the use of Sol-Gel. See e.g.,Jingyun Wang, et. al., Morphology and Entrapped Enzyme Performance inInkjet-Printed Sol-Gel Coatings on Paper, 26 Chem. Mater. 1941 (2014),incorporated herein by reference. However, other application techniquesof Sol-Gel can be used such as dot-matrix printing, screen printing,coating, automated pipettes, stamping, or spraying.

The channels for these immunoassays may also be created in a number ofways. One simple method for creating the channels is through the use ofimpact techniques where indentations are created in the material inwhich the immunoassays can be added. In these embossing techniques, theindentations form channels that direct liquid to flow through to theimmunoassays. Additionally, embossing techniques can be used to createbarriers by varying the density of the device material whereby denser,hydrophobic channel walls are created that direct the flow of the samplethrough the channels. Another way that the channels can be created isthrough printing methods. For example, inkjet printable sol-gelmaterials can be used to create hydrophobic barriers for these channelsin some embodiments. See e.g., Jingyun Wang, et. al., Morphology andEntrapped Enzyme Performance in Inkjet-Printed Sol-Gel Coatings onPaper, 26 Chem. Mater. 1941 (2014).

One of skill in the art would recognize a number of advantages inintegrating the testing channels and immunoassays into the deviceitself. This technique avoids the use of nitrocellulose test stripswhich are used in many devices in the market. By avoiding the use of thenitrocellulose test strips, and integrating the entirety of the deviceinto a single material, the manufacturing process is simplified.Additionally, the nitrocellulose test strips are not flushable, which isa significant barrier to creating an entirely flushable strip.

In the embodiment demonstrated in FIG. 1, the urine volume indicator 2provides for a visual indication of the sufficiency of the sample.Persons of skill in the art would recognize this feature as advantageousover ways of indicating volume sufficiency in existing applications inwhich the user is expected to count anywhere from five to 30 seconds inhis or her head to understand when the device has a sufficient volume offluid sample. Having a volume indicator 2 integrated into the devicealso avoids the use of electronic equipment within the device toindicate when a sufficient fluid level is achieved. There also existdevices that have color changing properties to indicate that the deviceis in contact with fluid, but such devices do not indicate if theappropriate volume is achieved. The volume indicator 2 in FIG. 1 can beachieved in a number of ways including through the use of a hydrochromicink portion as part of the urine-based diagnostic device that isdesigned to complete its hydrochromic transformation when enough fluidsample of the urine is achieved for the diagnostic to perform optimally.Hydrochromic inks react to fluid by modifying the appearance of theircolor. The design of this in relation to the device could, in someembodiments, be linear and communicate as part of the user interface.Its transformation from one color to another would indicate as a visualtool to the user that a satisfactory amount of fluid sample is on andwithin the diagnostic device. While hydrochromic ink may be used in apreferred embodiment of the device, other volume indicators can be usedincluding hydrochromic paint, a chromatic assay, an acid/base reactivetest, dispersing an ink or paint when wet, the appearance of an elementwhen the testing material becomes translucent or transparent when wet,or through the use of chemically sensitive materials. One example of achemically sensitive material is the use of humidity sensitivenanofibers. See e.g., Mogera, U. et. al., Ultrafast Response HumiditySensor Using Supramolecular Nanofibre and its Application in MonitoringBreath Humidity and Flow, 4 Sci. Rep. 4103 (2014), incorporated hereinby reference.

The embodiment depicted in FIG. 1 also includes a perforation 4. Thisperforation is designed such that the soiled portion of the device usedto collect the sample can be discarded by the user while awaiting theresults without affecting the readout. A person of skill in the artwould recognize this as advantageous for a number of reasons includingreducing the size of the test to be discarded to aid in flushability aswell as allowing the user to discard the soiled portion of the devicewhile awaiting results for sanitary reasons.

The embodiment in FIG. 1 further comprises an embossed collection pad 5.This collection pad 5 is designed in such a way to increase the surfacearea of the collection portion of the device and aid in the flow ofsample to the testing portion of the device. To increase flow to thetesting portion of the device, it would be beneficial for the channelsin the embossed pattern to be oriented vertically, i.e., parallel to theimmunoassay channels. However, the embossed pattern can be designed in anumber of ways to adjust the time it takes for the sample to reach thechannels. By adjusting the embossed pattern, one could design the deviceto return a fast result without having the sample move so fast that itwashes the biorecognition agents out of the immunoassays. In this way,one can control the speed at which the device returns the result.

In other embodiments of this invention, the entirety of the device canbe flushed or is water dispersible which provides an optional layer ofprivacy for users not wanting their results to enter the landfill orrecycling bound municipal waste systems. Flushability is determined bythe device's form and materiality, though there are multiplecombinations of the two. The constraints of the device could becharacterized as being small enough in depth and width to pass throughall standard plumbing. In an exemplary embodiment, the material isformed from cellulose fibers in compressed or non-woven format and mayinclude binding materials like polyvinyl alcohol, although other typesof materials can be used. The non-woven formats can be created by anumber of different processes including either wet laid or air laidoperations. Wet laid and air laid nonwoven techniques are well known inthe art. See e.g., EP0321237 B1 incorporated herein by reference.Additionally, the cellulose pulp fibers can be hydroentangled in orderto prevent degradation during use of the device while still maintainingflushability. However, while cellulose mixtures are preferred, theinvention is not limited to this material as long as the selectedmaterial satisfies the flushability requirements. One such suitablematerial for use in this application is available from SuominenCorporation under the trade name HYDRASPUN™. The combination shoulddissolve to the standards and guidelines set out in the “Guidelines forAssessing the Flushability of Disposable Nonwoven Products: A Processfor Assessing the Compatibility of Disposable Nonwoven Products withPlumbing and Wastewater Infrastructure. Third Edition. August 2013. ©2013 IVDA and EDANA.”

In another embodiment of the invention, the device may be adjusted or isflexible for the purposes of user interaction and personalization,packaging, and transportation. Persons of skill in the art wouldrecognize that in order for women to urinate on a midstream diagnosticdevice, some level of aiming on the part of the user is necessary,creating an opportunity for misuse or confusion on the part of the user.Culturally, women are not expected to aim their urine stream in manycases and a flexible solution gives opportunity for user adjustment anduser personalization to accommodate the flow and directionality of theirurine stream. The action of collecting urine by a midstream device canbe simplified by a more dynamic design that allows for greater usercontrol. The flexibility of the device can be adjusted based on thematerial being used. For example, non woven materials can be made moreor less flexible based on the way in which the fibers are bound, the wayin which the material is manufactured, and the additives added to thecellulose materials. More specifically, increased rigidity of thenon-woven material can be accomplished through a number of methodsincluding but not limited to compression molding or the addition ofwater dispersible hardeners such as wet strength resins. In someembodiments, the device can be highly flexible, while in others thedevice can be more rigid in nature. For example, based on the non-wovenmaterial or techniques being used, the device can be designed to beadjusted into a desirable form—by the user or others—prior to usewhereupon it may keep its form through the sample collection process. Inthis way, the form of the device can be personalized depending on theuser.

In another embodiment of the invention, the device is foldable. By beingfoldable, the device may be more easily packaged and transported.Additionally, a foldable device aids in discretion as it can reduce thesize of the device allowing for discrete carrying. A foldable embodimentof the device is demonstrated in FIGS. 5, 6, and 7. In these examples,the device has two fold lines 13 such that the device's surface area canbe reduced for more discrete carrying and for packaging. However, therecan be any number of fold lines depending on what size folded device isdesired. Additionally, the integrated manner in manufacturing thisdevice into a single material is what allows the foldable property to bepossible without affecting the integrity of the device.

FIG. 2 depicts another embodiment of the device in which the deviceutilizes both a “regular” or “sandwich” assay 7 as well as a“competitive” assay 8 as well as a volume indicator 6. A “regular” or“sandwich” assay 7 is used to show a chromatic visual readout when thespecified element or hormone is present. These can take on a number offormats including lateral flow or vertical flow tests. Persons of skillin the art would recognize that this regular assay, also called anenzyme-linked immunosorbent assay (ELISA), is commonly used in currenttesting devices, such as many pregnancy testing kits currently on themarket. In this regular assay, a biorecognition agent is used to bind toa selected analyte in order to give a visual readout when it is presentat a predetermined concentration. In this context, the chromatic visualreadout would not occur if the specified element or hormone were notpresent. In a “competitive” assay 8, this scenario is reversed from theperspective of the user. An additional phase to the assay is includedthat contains a form of the specified element or hormone with aconjugated enzyme. Should the specified element or hormone exist in thecollected urine sample, it may travel through the channels of the assay“competing” with the modified elements with conjugated enzymes forantibodies with which to bind. In this scenario, the color change wouldnot occur and the visual readout would not be displayed to the user.Should the specified element or hormone not exist in the collected urinesample, the modified elements with conjugated enzymes would have no“competition” for antibodies with which to bind and would produce acolor changing visual readout for the user. This embodiment of theinvention includes the feature of having both of these types of assayscoexisting in a single urine-based diagnostic device. One example ofthis would be in a pregnancy test that a pregnant woman would get avisual diagnostic readout indicating the presence of the hormone hCG(human chorionic gonadotrophin) yet a non-pregnant woman would also geta visual diagnostic readout indicating the lack of hCG.

FIG. 8 depicts another embodiment in which the device utilizes a control14, a first immunoassay 15, a second immunoassay 16, and a thirdimmunoassay 17 in the same channel, a volume indicator 18, two foldlines 19, and an embossed collection pad 20. In this embodiment, themultiple immunoassays are configured to test for different analytes. Forexample, the first immunoassay can be designed to detect for hCG at apredetermined level, the second immunoassay can be designed to detectfor glucose at a predetermined level, and the third can be designed todetect for luteinizing hormone. In this way, the device can test for thepresence of three different analytes using a single sample. However,this embodiment of the invention is not limited to this number ofimmunoassays or these analytes. The device can be configured with aplurality of immunoassays to test any number of analytes in order togive the desired number and type of results.

In further embodiments, the plurality of immunoassays can be designed totest for multiple levels of an analyte. For example, the device can beconfigured with three immunoassays each testing for a differentconcentration of hCG, such as 25,000 mIU/ml, 7,000 mIU/ml, and 25mIU/ml. In this example, the device could indicate not only a positiveresult for pregnancy, but could approximate the period of time the userhas been pregnant. By testing for multiple volumes of an analyte, theuser could also be given an approximate range for the amount of analytein the sample. The number of immunoassays being used in the device andthe levels being tested for can be varied based on what type ofinformation the device needs to return—a higher number of immunoassaystesting for smaller analyte volume intervals may return more accurateestimations of the volume of the target analyte in the sample.

FIG. 3 depicts another embodiment of the device which utilizes a controlindicator 9, a positive readout 19, a volume indicator 11, an embossedcollection area 12, and fold lines 13. In this embodiment, the controlindicator 9 and positive readout 10 are situated in a lineararrangement. The volume indicator 11 is designed to allow the user toknow when sufficient sample volume is achieved. The embossed collectionpad 12 aids in directing flow to the channels. The fold lines 13 enablethe user to fold the device to a smaller size for easier and morediscrete carrying.

FIG. 4 depicts another embodiment of the device in which the diagnosticreadout is represented using words or language. Persons of skill in theart would recognize that this adds a level of clarity and ease-of-useover existing devices which rely on lines, squares, or patterns or onelectronic materials to provide a readout in written language. Thedevice includes a feature that allows for a non-electronic device tohave a word or language readout of the diagnostic results. Themicrofluidic channels are designed in a way that the color changingportions of the diagnostic assay are positioned into a patternresembling words. One example would be for the device to have theantibodies in a designed channel so that, if the diagnostic werepositive, a pregnancy could convey this in the written word “Pregnant”.

FIG. 9, depicts another embodiment of the device in which the visualreadout is displayed using a graphic design or other pictorialrepresentation. By using a recognizable graphic representation of theresults of the test, the ease-of-use of the device is enhanced. Thisdesign is achieved by designing the microfluidic channels is the form ofthe desired graphic. In the embodiment displayed by FIG. 9, the deviceutilizes a baby's face to indicate a positive pregnancy test result.However, other graphics or pictorial representations can be used basedon what type of analyte the device is configured to detect.

The various embodiments of the invention are designed for an untrainedperson (although not limited to use by such a person) to use the deviceto test for a selected analyte or condition. The user of the device,after adjusting its flexible form to aid in sample collection, can addthe urine sample to the collection portion of the device, possibly byurinating directly onto the device. The sample may then travel throughthe testing portion of the device before the device returns a visualresult.

What is claimed is:
 1. A device for use with a fluid sample, comprisinga biodegradable diagnostic device having a diagnostic channel integratedinto the device material, wherein the diagnostic channel is formed of abiodegradable material and includes a biorecognition specific for ananalyte in the fluid sample.
 2. The device of claim 1, wherein thedevice is water-dispersible.
 3. The device of claim 1, wherein thebiodegradable material is a flushable material.
 4. The device of claim1, wherein the device is flushable.
 5. The device of claim 2, whereinthe diagnostic channel and the body are composed of cellulose.
 6. Thedevice of claim 2, further comprising an embossed pattern on the body orthe diagnostic channel.
 7. The device of claim 1, wherein thebiorecognition agent is an immunoassay reagent.
 8. The device of claim1, wherein the biorecognition agent comprises multiple biorecognitionagents, each capable binding a different analyte, if present, in thefluid sample.
 9. The device of claim 2, wherein the diagnostic channeland the body are comprised of the same water-dispersible material. 10.The device of claim 1, wherein the device is a hand-held device.
 11. Thedevice of claim 1, wherein the biodegradable material comprises anonwoven material.
 12. A device for use with a fluid sample, comprisinga biodegradable diagnostic device capable detecting an analyte in thefluid sample, wherein the biodegradable diagnostic device has adiagnostic channel formed of a biodegradable material.
 13. The device ofclaim 12, comprising a body formed of a water-dispersible material,wherein the diagnostic channel is positioned in the body.
 14. The deviceof claim 12, wherein the biodegradable material is a flushable material.15. The device of claim 12, wherein the biodegradable diagnostic devicecapable detecting an analyte in the fluid sample includes abiorecognition agent.
 16. The device of claim 12, wherein the device iswater dispersible.
 17. The device of claim 12, wherein the biodegradablematerial comprises a nonwoven material.
 18. A lateral or vertical flowdiagnostic device of the type capable of detecting an analyte in a fluidsample, characterized in that the diagnostic device is comprisedentirely of a biodegradable material.
 19. The lateral or vertical flowdiagnostic device of claim 18, wherein the lateral or vertical flowdiagnostic device comprises an immunoassay device.
 20. lateral orvertical flow diagnostic device of claim 18, wherein the biodegradablematerial is a water-dispersible material.